Randomized phase III trial of amrubicin versus topotecan as second-line treatment for patients with small-cell lung cancer.

Abstract

PURPOSE:

Amrubicin, a third-generation anthracycline and potent topoisomerase II inhibitor, showed promising activity in small-cell lung cancer (SCLC) in phase II trials. This phase III trial compared the safety and efficacy of amrubicin versus topotecan as second-line treatment for SCLC.

PATIENTS AND METHODS:

A total of 637 patients with refractory or sensitive SCLC were randomly assigned at a ratio of 2:1 to 21-day cycles of amrubicin 40 mg/m(2) intravenously (IV) on days 1 to 3 or topotecan 1.5 mg/m(2) IV on days 1 to 5. Primary end point was overall survival (OS); secondary end points included overall response rate (ORR), progression-free survival (PFS), and safety.

RESULTS:

Median OS was 7.5 months with amrubicin versus 7.8 months with topotecan (hazard ratio [HR], 0.880; P = .170); in refractory patients, median OS was 6.2 and 5.7 months, respectively (HR, 0.77; P = .047). Median PFS was 4.1 months with amrubicin and 3.5 months with topotecan (HR, 0.802; P = .018). ORR was 31.1% with amrubicin and 16.9% with topotecan (odds ratio, 2.223; P < .001). Grade ≥ 3 treatment-emergent adverse events in the amrubicin and topotecan arms were: neutropenia (41% v 54%; P = .004), thrombocytopenia (21% v 54%; P < .001), anemia (16% v 31%; P < .001), infections (16% v 10%; P = .043), febrile neutropenia (10% v 3%; P = .003), and cardiac disorders (5% v 5%; P = .759); transfusion rates were 32% and 53% (P < .001), respectively. NQO1 polymorphisms did not influence safety outcomes.

CONCLUSION:

Amrubicin did not improve survival when compared with topotecan in the second-line treatment of patients with SCLC. OS did not differ significantly between treatment groups, although an improvement in OS was noted in patients with refractory disease treated with amrubicin.

• Authors: Joachim von Pawel, Robert Jotte, David R Spigel, Mary E R O'Brien, Mark A Socinski, Jörg Mezger, Martin Steins, Léon Bosquée, Jeffrey Bubis, Kristiaan Nackaerts, José M Trigo, Philip Clingan, Wolfgang Schütte, Paul Lorigan, Martin Reck, Manuel Domine, Frances A Shepherd, Shaoyi Li, Markus F Renschler
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 32 Issue 35 Pg. 4012-9 (Dec 10 2014) ISSN: 1527-7755 [Electronic] United States
• PMID: 25385727 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 by American Society of Clinical Oncology.

Chemical References

• Anthracyclines
• Antineoplastic Agents
• Topotecan
• amrubicin
• NAD(P)H Dehydrogenase (Quinone)
• NQO1 protein, human

Topics

• Adult
• Aged
• Aged, 80 and over
• Anthracyclines (administration & dosage)
• Antineoplastic Agents (administration & dosage)
• Disease-Free Survival
• Female
• Genotype
• Humans
• Kaplan-Meier Estimate
• Lung Neoplasms (drug therapy, mortality)
• Male
• Middle Aged
• NAD(P)H Dehydrogenase (Quinone) (genetics)
• Odds Ratio
• Polymorphism, Single Nucleotide
• Proportional Hazards Models
• Small Cell Lung Carcinoma (drug therapy, mortality)
• Topotecan (administration & dosage)
• Treatment Outcome
• Young Adult